Our goal is to locate and characterize areas in the vascular and intestinal systems of the dog which cause autonomic reflex alteration of the secretion rates of pancreatic hormones when they are stimulated with glucose or related substances. The availability of an innervated, but otherwise isolated, cross-perfused pancreas permits us to examine the influence of the autonomic nerves on the secretion rate of insulin, and other hormones, without interference from confounding humoral stimuli. Since in the proposed double-dog cross-perfusion experiments the only functional connection between the body of the small dog and its pancreas will be its autonomic nerves, infusions into its vascular or intestinal systems can cause changes in the insulin secretion rate only by way of the nerves. There is evidence that reflexogenic areas exist in the vascular beds of the carotid arteries and the liver, and in the small intestine. These areas will be tested in separate experiments. When a reflexogenic area is found, its sensitivity and specificity will be examined by infusing into it different doses of glucose and related compounds (galactose, 3-0-methyl-glucose). The afferent and efferent pathways of the reflex will be determined. In selected experiments, secretion rates of glucagon, gastrin and somatostatin will be calculated. Secretion rates will be calculated by assaying the immunoreactive hormone concentrations in the pancreatic effluent and pancreatic arterial plasma, and measuring the plasma flow through the organ. Glucose concentrations will be assessed in the arterial plasma of the pancreas and the small dog, using an automated glucose oxidase method. This work may result in better understanding of the mechanisms responsible for disordered glucose metabolism in a number of human diseases.